Pressure-sensitive adhesive compositions suitable for medical uses

ABSTRACT

A dermatologically-acceptable, moisture vapor-permeable, pressure-sensitive adhesive composition that is a single-phase solid at ambient temperature and resists dissolution when exposed to water, comprises a polymer adhesive which is the product of a process comprising the steps of chain extending a water-soluble derivatized capped prepolymer which comprises a first terminal group and a low-temperature curable group, until the resultant polymer attains a determined level of tackiness, and then subjecting the polymer to low-temperature curing. The adhesive is used to advantage in medical products like adhesive bandages, plasters, dressings and surgical drapes, and can dissolve water-soluble bio-active additives.

BACKGROUND OF THE INVENTION

The present invention relates to adhesive materials, and particularly toa new group of dermatologically acceptable, moisture vapor-permeable,pressure-sensitive adhesive compositions which can be used in variousmedical contexts, including as a component of a wound dressing.

Wound management has developed rapidly in recent years due to advancesin the understanding of the wound healing process and to the advent ofnew materials and techniques for use in wound dressings. In particular,much activity has occurred in the development of pressure-sensitiveadhesive, moisture vapor-permeable wound dressings. These wounddressings provide coverings that protect wounds from further harm,enhance the natural healing process, and prevent bacterial invasion.Despite the availability of these newly-developed materials, infectionis still a common complication associated with conventional dressings.

A wound is a loss of continuity of skin or mucous membrane due toaccidental injury or planned surgery. Wound healing is essentially thereplacement of dead or damaged tissue by healthy, living cells. Healingcan occur either by partial or complete regeneration or by repair.Regeneration implies complete restitution to regain the original tissuestructure. Repair, on the other hand, involves formation of a newpermanent structure, a scar. Wound healing is typically a two-stepprocess, involving regeneration of epithelial tissue and repair ofconnective tissue.

Among the various factors which affect wound healing are, for example,host resistance, environment and location of the wound, and the presenceof bacteria. The patient's overall health, metabolic and nutritionalstatus determine resistance. Blood flow, lymphatic drainage, temperatureand humidity are important in respect of the environment and location ofa wound. Bacteria at the wound site can proliferate and cause infection.

Wound dressings should possess a number of important characteristics inorder to protect the wound and enhance its ability to heal. An idealwound dressing should (i) have optimal water permeability to preventdesiccation of the wound and fluid accumulation under the covering; (ii)prevent microbial invasion from the environment; (iii) have no antigenicproperties; (iv) be an elastic-plastic film to facilitate intimatecovering of all possible contours of the human body; (v) be capable ofboth adhering well to the wound and being readily removable withoutcausing any damage to the tissue beneath the covering; and (vi) beinexpensive to produce and readily amenable to storage.

Modern wound dressings are generally constructed of a backing sheet witha pressure-sensitive adhesive on one side. The backing sheet istypically moisture vapor permeable, allowing water vapor to escape fromthe wound site while preventing liquid water from entering or escapingfrom the site. In addition, bacteria are prevented from passing throughthe wound dressing. The adhesive provides the desired pressure-sensitiveadherence for securing the backing to the wound site and retaining thebacking in the desired position.

High moisture vapor-permeability of a dressing prevents maceration ofthe skin due to occlusion of transepidermal fluid lost from the body anddelamination of the dressing from the wound site, as will be explainedbelow. Many modern wound dressings are known for their high moisturevapor-permeability, as measured by the moisture vapor transmission rate(MVTR). For example, U.S. Pat. Nos. 4,340,043 and 4,360,369 disclose anadhesive-coated, polymeric sheet material having a high MVTR. Thismaterial is commercially available as a wound dressing marketed, underthe mark Op-Site®, by Nephew & Smith, Ltd. See also U.S. Pat. No.4,233,969.

The moisture permeability of such dressings is a function of themoisture permeability of both the polymeric film and thepressure-sensitive adhesive used. Many wound dressings use moisturepermeable adhesives. For example, U.S. Pat. No. 3,645,835 (Hodgson)discloses both a moisture vapor-permeable backing material and amoisture vapor-permeable pressure-sensitive adhesive. The Hodgson patentalso teaches that both the backing material and adhesive are unaffectedby water, i.e., they neither swell nor absorb water. U.S. Pat. Re. No.31,887, a reissue of the Hodgson patent, specifically discloses thebacking material as a polyurethane and the adhesives as a polyvinylethyl esters or an acrylate. See also U.S. Pat. No. 4,638,797.

Polyurethane adhesives have been developed which are suitable for wounddressings. For example, U.S. Pat. No. 3,796,678 discloses a polyurethaneadhesive which is highly branched and isocyanate-blocked withmonofunctional alcohols. U.S. Pat. No. 4,626,475 relates to apolyurethane having improved adhesive properties, accomplished by usinga bicyclic amide acetal additive. Aqueous-based polyurethane adhesiveshave also been developed. See, for example, U.S. Pat. Nos. 4,442,259 and4,507,430. As explained above, the overall goal of wound dressings is toprevent infection and to provide an environment that promotes woundhealing. To prevent infections, modern wound dressings are continuous,or occlusive, that is, there are no openings in the dressing throughwhich bacteria from the environment can reach the wound site. Even withan occlusive dressing, however, infection may occur at the wound site ifthe dressing loses its integrity or if bacteria are already present atthe wound site or the surrounding skin. Loss of integrity allowsmicrobes from the environment to reach the wound site and causeinfection. Bacteria already present at a wound site can also proliferateand cause infection.

The principle cause of integrity failure of an occlusive film dressingis delamination of the dressing from the wound site. Delamination is afunction of the moisture permeability of the dressing and the ability ofthe dressing to absorb fluid. If the dressing does not have a highenough MVTR, then fluid from the wound or surrounding skin canaccumulate. If the pressure-sensitive adhesive used neither absorbs thisfluid nor allows it to reach an absorbent layer, then delaminationbetween the pressure-sensitive adhesive and the wound site and/orsurrounding skin will occur. If the delamination reaches the edge of thedressing, loss of dressing integrity results in the wound site beingexposed to environmental microbes, i.e., loss of the bacterial barrier.The integrity of a dressing thus, is a function of both its moisturevapor permeability and fluid swellability. One of the major problemswith current wound dressings is the use of materials with aninsufficiently high MVTR to avoid delamination and pressure-sensitiveadhesives unable to absorb fluid.

Attempts have been made to develop water-swellable adhesives byincorporating various substances into the adhesive which absorb water.Most of these attempts utilize gel adhesives. For example, U.S. Pat. No.4,661,099 discloses a water-absorptive polyurethane gel adhesive whereinpolyols are immobilized in the cross-linked polyurethane. U.S. Pat. No.4,367,732 relates to a polystyrene-based gel adhesive in whichwater-swellable hydrocolloids are dispersed. See also U.S. Pat. No.3,648,835 and Re. No. 31,887. Upon absorbing water, such gels tendthemselves to dissolve in the water. Gel adhesives generally lack theinherent stability and storage convenience of solid adhesives. See alsoU.S. Pat. Nos. 4,233,969, 4,156,066 and 4,156,067, directed topolyurethane films that are water-swellable.

Even if a dressing maintains integrity, the enclosed environmentprovided by dressings may allow bacteria present at the wound site onthe surrounding skin to multiply unduly and lead to infection. Numerousbacteria are present on human skin. Some may survive an initialapplication of a topical antimicrobial agent and act as seeds forsubsequent growth. Continuous application of an antimicrobial agentwould be highly desirable.

Recently, several wound dressings have been developed wherein anantimicrobial agent is applied or added to the polymeric film or, morepreferably, to the adhesive. For example, U.S. Pat. Nos. 4,554,317 and4,643,180 disclose application of an agent to the surface of a membraneor adhesive, respectively. Other attempts have been directed to theformation of a chemical complex between the antimicrobial agent and thefilm or adhesive. U.S. Pat. Nos. 4,542,012 and 4,323,557 teachcomplexing iodine with polyvinylpyrrolidone residues in polymer. Releaseof the antimicrobial agent depends, however, on its appropriatedissociation from the chemical complex.

Still other prior art dressings teach a physical combination of theantimicrobial agent and polymer or adhesive. For example, U.S. Pat. No.4,614,787 discloses a pharmacologically active agent dispersed through acured polymeric film to which an adhesive may be applied. U.S. Pat. No.4,310,509 discloses a flexible-backing material to which is applied acomposition of a broad-spectrum antimicrobial agent homogeneously andstably dispersed in a pressure-sensitive adhesive. U.S. Pat. No.4,460,369 discloses an adhesive-coated, liquid-impervious, moisturevapor-permeable, thin polymer sheet in which a solid antibacterialmaterial in a finely divided form is incorporated within the adhesive.U.S. Pat. Nos. 4,156,066 and 4,156,067 disclose that a medicament may beadded to a lactone-modified polyurethane which is applied to the skin asa film. See also U.S. Pat. Nos. 3,896,789 and 3,769,071, which discloseaddition of other bioactive agents, such as retinoic acid and5-fluorouracil, to a polyurethane adhesive.

A problem inherent in these prior art attempts is that since mostadhesives are not water-soluble, water-soluble antimicrobials may onlyexist as a separate phase dispersed throughout the adhesive. Forexample, the Berglund Pat. discloses that if an antimicrobial iswater-soluble and is in a water solution, a stable water-in-oil emulsionis formed upon mixing with the adhesive. If, on the other hand, anantimicrobial is soluble in an organic solvent and is in solution inthat solvent, and the organic solvent is miscible with the adhesivesolution, then the solvent of the adhesive extracts the solvent of theantimicrobial solution, causing the antimicrobial to separate out asdistinct, minute, separate phase particles.

Still another approach utilizes adhesives in which the bioactive agentcan be truly dissolved in the adhesive. For example, U.S. Pat. Nos.4,307,717 and 4,675,009, both issued to Hymes et al., disclose aflexible backing material provided with a hydrophilic, adhesive matrixwhich has a solid phase of a polysaccharide and a liquid phase of analcohol, carbohydrate and/or protein, where a medicinal agent is"molecularly dispersed," rather than encapsulated, in the matrix. TheHymes '009 Pat. is a continuation-in-part of the '717 Pat. and statesthat the adhesive is capable of absorbing moisture and that themedicinal agent is "molecularly dissolved and/or suspended" in theadhesive matrix.

Despite recognition of the many practical wound dressing designproblems, proper solution to all these problems in a single wounddressing has not been demonstrated in the prior art. Despiteimprovements in modern wound dressings, dressing materials are neededthat comprise higher-MVTR compositions and pressure-sensitive adhesives.The MVTR of a pressure-sensitive adhesive is usually the limiting factorin the total moisture permeability of a film-backed dressing. Moreover,even though adhesives should optimally absorb or transport fluid, nearlyall medically suitable, pressure-sensitive adhesives which are currentlyavailable are unaffected by water, i.e, they neither swell nor absorbwater.

While effective to some degree, conventional wound dressings whichincorporate drugs and other bioactive agents in a pressure-sensitiveadhesive layer are generally limited to solvent-based (rather thanaqueous-based) antimicrobial agents or drugs, since mostpressure-sensitive adhesives are hydrophobic. When water-soluble agentsare placed within these adhesive systems, water-in-oil emulsions form orthe agents precipitate out as solid particles. Release of the agentrequires diffusion of particulates through a hydrophobic matrix.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to provide afilm-backed adhesive material which includes a pressure-sensitivepolyurethane adhesive characterized by a unique balance of bothhydrophilic and hydrophobic characteristics, such as moisturevapor-permeability, an ability to absorb fluid without dissolving, and acapability to dissolve water-soluble agents in a solid solution, ratherthan forming an emulsion or precipitate.

It is also an object of the present invention to provide a medicallysuitable, pressure-sensitive adhesive that has a very high moisturevapor-permeability and, thus, minimizes fluid accumulation due totrapped moisture beneath the adhesive.

It is additionally an object of the present invention to provide apressure-sensitive adhesive that swells without dissolving on exposureto water or other body fluids and, thus, minimizes delamination betweenthe wound site and adhesive due to fluid accumulation.

It is a further object of the present invention to provide apressure-sensitive adhesive within which water-soluble bioactive agentsmay be dissolved.

It is yet another object of the present invention to provide a methodfor the ready preparation of a wound dressing, which method canaccommodate the use of water-soluble, bioactive agents without thedisadvantages of precipitation and emulsion-formation discussed above.

In accomplishing the foregoing objects, there has been provided,according to one aspect of the present invention, an adhesivecomposition which comprises a polymer adhesive that is soluble ordispersible in water and is low-temperature curable to form a solidwhich is single-phase at ambient temperature, pressure-sensitive,dermatologically acceptable, moisture vapor-permeable and resistant todissolution when exposed to water. The adhesive composition preferablycontains a bioactive agent dissolved therein.

In a preferred embodiment, the polymer adhesive is the product of aprocess comprising the steps of (A) reacting a prepolymer compoundcomprising a plurality of hydroxyl groups and a polyisocyanate cappingagent to form an isocyanate-terminated capped prepolymer comprisingpolyurethane units; (B) reacting a portion of the terminal isocyanategroups of the capped prepolymer with a derivatizing agent comprising agroup reactive with isocyanate, in particular a hydroxyl group, and alow-temperature curable group to form a derivatized capped prepolymer;and (C) reacting the derivatized capped prepolymer with a chainextension agent reactive with isocyanate, in particular with water, toeffect chain extension of the derivatized capped prepolymer, whereby apolymer is formed, until the polymer attains a determined level oftackiness, at which point chain extension is halted by addition of achain termination agent reactive with isocyanate.

In accordance with another aspect of the present invention, there isprovided a cured adhesive composition comprising a polymer adhesivewhich is the product of a process comprising the steps of (A) providinga water-soluble derivatized capped prepolymer, (B) subjecting thederivatized capped prepolymer to chain extension to form a polymer,until a determined level of tackiness is attained, wherein a chaintermination agent is added, and (C) subjecting the polymer tolow-temperature curing. Preferably, a bioactive agent is dissolved inthe adhesive.

In accordance with yet another aspect of the present invention, there isprovided a water vapor-permeable, pressure-sensitive adhesive wounddressing, comprising a flexible backing coated with a pressure-sensitiveadhesive layer provided on at least a portion of the surface of thebacking, wherein the adhesive layer comprises a cured adhesivecomposition as described above, preferably comprising a bioactive agentdissolved therein.

In accordance with a further aspect of the present invention, there isprovided a process for producing a wound dressing as described above.

In accordance with yet a further aspect of the present invention, thereis provided a process for producing an uncured polymer adhesive asdescribed above.

In accordance with still another aspect of the present invention, thereis provided a process for producing a cured polymer adhesive asdescribed above.

Other objects, features and advantages of the present invention willbecome obvious to those skilled in the art from the following detaileddescription. It should be noted, however, that the detailed descriptionand specific examples, while indicating preferred embodiments of thepresent invention, are given by way of illustration and not limitation.Many changes and modifications may be made within the scope of thepresent invention without departing from the spirit thereof, and theinvention includes all such changes.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In the following description of the present invention, process steps arecarried out at room temperature and atmospheric pressure unlessotherwise specified. The phrase "pressure-sensitive adhesive" means thata composition thus qualified is inherently tacky, viscoelastic andcohesive in its dry (cured) state. The expression "aqueous-based" refersto a solvent or carrier which is water or a mixture of water and amiscible solvent such as an alcohol. The term "low-temperature curable"refers to groups which are capable of cross-linking under the influenceof actinic radiation, which includes ultraviolet light and electronemission, as well as free radicals, pH shift or other mechanisms whichare capable of functioning at approximately room temperature. The term"polyfunctional" is used with reference to a compound having two or morereactive groups, including low-temperature curable groups. A material is"dermatologically acceptable" if it does not cause noticeable skinirritation.

Polymer adhesives according to the present invention are preferablyobtained by treating a water-soluble compound, referred to as aderivatized capped prepolymer, which comprises a plurality of firstterminal groups and a plurality of low-temperature curable groups, witha second compound, referred to as a chain extension agent, which isreactive with the first terminal groups, resulting in formation of apolymer. The chain extension is terminated when the resulting polymerachieves a desired tackiness, by reacting the polymer with a thirdcompound, referred to as a chain termination agent, reactive with thefirst terminal group. Incorporation of the chain termination agent intothe chain halts further chain growth and completes formation of theuncured polymer adhesive. Preferably the derivatized capped prepolymeris reacted with an excess of the chain extension agent, based on thecontent of the first terminal group of the derivatized cappedprepolymer.

Preferably the first terminal group is an isocyanate group, in whichcase the chain extension agent is preferably water, a polyol or apolyamine. The first terminal group may also be an ester group, in whichcase the chain extension agent is preferably ammonia or a polyamine. Thefirst terminal group may also be an isothiocyanate group.

The chain extension is preferably conducted using at least a two-foldequivalent excess of the chain extension agent.

The chain extension reaction may be conducted at room temperature or atelevated temperatures of up to approximately 100° C. In general,temperatures of about 20° C to about 90° C. can be used to increase thereaction rate. Elevated temperature may be particularly advantageouswhere the derivatized capped prepolymer has been prepared using analiphatic polyisocyanate.

The chain extension reaction is allowed to proceed until the reactionmixture acquires a desired adhesive capability. The characteristics ofthe adhesive or adhesive capability are generally given in terms ofoptimal bonding strength for a given substrate or substrates at workableviscosity levels. Adhesive capability of the reaction mixture can betested qualitatively or quantitatively. Qualitative monitoring simplyinvolves removing samples from the reaction mixture and evaluating theiradhesive properties by touch or by an elementary test of adhesivenessbetween two substrates. In more quantitative procedures, the reactionmixture is monitored, for example, via measurement of viscosity.

In general, the viscosity of the reaction mixture increases as the chainextension reaction proceeds. Sufficient correlation may be establishedbetween the viscosity of the reaction mixture and its adhesivecapability to permit the use of viscosity measurements as a means ofmonitoring the reaction. Useful viscosities may vary over a wide range,depending on such factors as the nature of the derivatized cappedprepolymer, the percent solids of the reaction mixture, and thetemperature of the reaction mixture.

A chain termination agent may be added to control the chain extension ofthe derivatized capped prepolymer, that is, to slow the reaction andprevent gelation of the derivatized capped prepolymer, before completetermination of the polymerization. The amount of chain termination agentused depends on such factors as the comparative reactivities of thechain extension agent and the chain termination agent with thederivatized capped prepolymer, and the desired rate of reaction. Themonofunctional chain termination agent used to control chain extensionof the derivatized capped prepolymer may be any compound capable ofreacting with the first terminal group so as to retard or prevent itsreaction with the chain extension agent. A variety of monofunctionalchain termination agents are suitable. Where the first terminal group isan isocyanate group, suitable monofunctional chain termination agentsinclude alcohols, such as methanol, ethanol, isopropanol and phenol;primary or secondary monamines like ammonia, methylamine, ethylamine andisopropylamine; oximes such as acetone oxime, butanone oxime,cyclohexanone oxime; and alkanol amines like ethanol amine. Inaccordance with another aspect of the present method, a combination oftwo or more monofunctional chain termination agents can be used. Anexample of such a combination, used where the first terminal group is anisocyanate group, is that of an alcohol with a more reactive chaintermination agent, such as an oxime. The alcohol in the combination mayprovide some chain termination function but is used primarily as adiluent or co-solvent, while the more reactive chain termination agentprovides the major proportion of the reaction with the isocyanate group.

In addition to alcohols, other co-solvents may be employed pursuant tothe present invention. These co-solvents should be miscible with wateror a water-alcohol mixture and, unless intended for use as amonofunctional chain termination agent, should be inert to the firstterminal groups. Preferred co-solvents are volatile solvents, such asacetone or methyl ethyl ketone, the use of which can facilitate dryingof the adhesive compositions. The co-solvent may be added prior, during,or subsequent to chain extension.

When the desired viscosity and/or adhesive capability has been attained,additional monofunctional chain termination agent, e.g., the chaintermination agent used for reaction control or a second, different agentreactive with the first terminal group, is added to the reaction mixturein an amount at least equal to or substantially greater than the amountof unreacted first terminal groups in the derivatized capped prepolymer,on an equivalent basis. The amount of unreacted first terminal groupsremaining in the derivatized capped prepolymer at the time the desiredadhesive capability is attained will vary with the nature of thederivatized capped prepolymer and the degree of chain extension.Although this amount can be measured, thereby allowing calculation ofthe minimum quantity of additional chain termination agent to be added,it is generally more convenient and satisfactory to simply employ anexcess amount of the chain termination agent.

By reaction of the additional chain termination agent with the remainingfirst terminal groups in the derivatized capped prepolymer, the chainextension reaction is terminated. The effectiveness of the chaintermination agent in terminating chain extension, i.e., the rate andextent of reaction with the remaining first terminal groups is increasedby using an excess amount of the agent and, consistent with suchincreased effectiveness, the resultant adhesive compositions tend tohave a longer shelf life. Reasonable excesses of the additional chaintermination agent, for example, in the range of a 10% to 100% equivalentexcess, in general do not adversely effect the adhesive capability.

The additional chain termination agent should be capable of forming areaction product with the first terminal group that is very stable towater, for reasonable periods of time at room temperature. Theadditional chain termination agent can be any of the aforementionedmonofunctional chain termination agents, or may be a polyfunctionalchain termination agent such as a diol, diamine or dioxime. Preferredchain termination agents are the more reactive monofunctional materials,exemplified by the aforementioned oximes and amines. It is also possibleto use ammonia. Although alcohols can be used as the additional chaintermination agent, and are often added in excess for such purpose andfor purposes of dilution, they are preferably employed in conjunctionwith a more reactive chain termination agent to insure a maximum shelflife for the product. For example, various primary and secondary aminesmay be used in conjunction with the alcohol; ammonia is particularlyuseful in this regard.

The additional chain termination agent may be added to the reactionmixture at any temperature up to about 100° C. Generally, the sametemperature used for chain extension is also used for this addition.

The derivatized capped prepolymer is preferably formed by reacting asecond water-soluble compound, referred to as a capped prepolymer, whichcomprises a plurality of the first terminal groups, with a derivatizingagent. The derivatizing agent comprises a first functional group whichis reactive with the first terminal groups, and a second functionalgroup which is low-temperature curable. The reaction is carried out suchthat a portion of the first terminal groups of the capped prepolymer arereacted with the first functional groups of the derivatizing agent,leaving the remainder of the first terminal groups available to reactwith the chain extension agent to effect polymerization.

The second functional group, i.e. the low-temperature curable group,preferably is curable under the action of actinic radiation, whichincludes ultraviolet radiation and electron emission, as well as pHshift or free radicals. In a preferred embodiment, the low-temperaturecurable group is an ethylenically unsaturated group, and particularlypreferably is an activated vinyl group.

Preferably, about 5 to 80% of the first terminal groups of the cappedprepolymer are reacted with the first functional group of thederivatizing agent. Particularly preferably, 5 to 50% of said firstfunctional groups are so reacted.

In a preferred embodiment, the first terminal group of the cappedprepolymer is an isocyanate group and the first functional group of thederivatizing agent is a hydroxyl or amine group. The derivatizing agentis preferably a hydroxyalkyl ester of a (C₁ -C₆)-α,β-unsaturatedcarboxylic acid. Suitable esters include hydroxyalkyl acrylates,methacrylates, crotonates and itaconates. The hydroxyalkyl ester ispreferably a hydroxyethyl ester, such as hydroxyethyl acrylate andhydroxyethyl methacrylate. Other examples of suitable acrylates include1,2,6-hexanetriol diacrylate, pentaerythritol triacrylate andneopentaerythritol triacrylate.

The first terminal group may also be an ester group, in which case thefirst functional group is preferably an amine group. In this embodiment,the derivatizing agent is preferably an aminoalkyl amide of a (C₁-C₆)-α,β-unsaturated carboxylic acid. Suitable amides include aminoalkylacrylamides, methacrylamides, crotonamides and itaconamides.

The capped prepolymer is preferably formed by reacting a polyfunctionalcompound, hereinafter referred to as a capping agent, which comprises aplurality of the first terminal group with a water-soluble prepolymerwhich comprises a plurality of a second terminal group reactive with thefirst terminal group. The capping agent reacts with the terminal groupsof the prepolymer, and thus "caps" the prepolymer with first terminalgroups on the terminal ends of the prepolymer.

In a preferred embodiment, the first terminal group is an isocyanategroup and the second terminal group is a hydroxyl group. This results information of a urethane capped prepolymer. These prepolymers areprepared by the well-known method of reacting a polyol with an aliphaticor aromatic polyisocyanate. Particularly preferably, the prepolymer is apolyoxyalkylene polyol or a polyester polyol. Carboxymethylcellulose canalso be used as the prepolymer. Excess polyisocyanate is usuallyemployed to insure reaction of all the polyol hydroxyl groups and tominimize crosslinking due to reaction of two or more isocyanate groupsof the same molecule.

Particularly preferred polyols used in accordance with the presentinvention are hydrophilic polyoxyethylene polyols, that is, hydrophilicpolyols comprising recurring oxyethylene (--CH₂ --CH₂ --O--) units.These polyols and the prepolymers prepared from them exhibit anespecially high degree of hydrophilicity, particularly those comprisingat least 20 mole %, more particularly at least 40 mole % oxyethyleneunits. Such polyols and prepolymers are therefore especially suitable,in terms of water solubility and reactivity, for use in accordance withthe present invention.

The advantages attendant to the hydrophilicity of the polyoxyethylenepolyols also extend to the adhesive materials in accordance with theinvention. Adhesive compositions can be prepared to have a relativelyhigh solids content, for example, as high as 60% on a weight basis, andhave favorable stability characteristics, i.e., minimal or no tendencyto form gels or to coagulate while sitting or to undergo phaseseparation. Also, the compositions can be readily diluted with polarsolvents such as water and alcohols.

The advantages realized by the use of hydrophilic polyoxyethylenepolyols and prepolymers are obtained without the use of surfactants,thus avoiding the presence of such materials and their effects onprocess steps of the present invention. Such surfactants are commonlynecessary for reactions of more hydrophobic prepolymers.

The use of excess capping agent, such as polyisocyanate, in preparingthe capped prepolymers will generally provide a composition containingunreacted capping agents. Chain extension of the resulting derivatizedcapped prepolymer thus entails reaction of the first terminal groups ofsuch unreacted capping agents.

Although polyisocyanates having an isocyanate functionality of three ormore may be used in preparation of prepolymers used herein, it isgenerally preferred to employ diisocyanates. Both aliphatic and aromaticdiisocyanates can be used. Suitable diisocyanates include:1,6-hexamethylene diisocyanate, isophorone diisocyanate,2,3,4-trimethyl-1,6-hexane diisocyanate, trimethylene di isocyanate,toluene-2,4-diisocyanate, diphenylmethane-4,4'-diisocyanate,biphenyl-4,4'-diisocyanate, and3,3'-dimethyl-4,4'-diisocyanate-1,1'-biphenyl.

Aliphatic polyisocyanates are preferred insofar as the resultantprepolymers generally react more slowly with water than those preparedfrom aromatic polyisocyanates. This permits better process control, andpossibly the use of less monofunctional chain termination agent.However, from the standpoint of minimizing reaction time, prepolymersprepared from aromatic polyisocyanates are preferred albeit in thepresence of a potentially greater amount of chain termination agent.Other considerations which might effect the choice of a particularpolyisocyanate include the hydrophobic/hydrophilic properties impartedto the resultant prepolymer and factors such as cost, availability andtoxicity.

In another preferred embodiment, the first terminal group is an estergroup and the second terminal group is an amine group. In thisembodiment, the prepolymer is preferably a polyaminoalkylene polyamine.

The prepolymer is preferably formed by reacting a first water-solublemonomer which comprises a plurality of the second terminal group with asecond water-soluble monomer which is reactive with the second terminalgroup. When the second terminal group is a hydroxyl group, the firstwater-soluble monomer is preferably a polyol and the secondwater-soluble monomer is preferably an epoxide compound such as ethyleneoxide or propylene oxide; these monomers react to form the preferredpolyoxyalkylene polyols. Suitable polyols include ethylene glycol,glycerol, trimethylolpropane and pentaerythritol, and also a mixture ofethylene glycol and glycerol. The prepolymer preferably has a molecularweight of about 3 to 15 kilodaltons. The resulting isocyanate cappedprepolymer has an NCO-value of 2.5-3.0, that is, the average cappedprepolymer comprises 2.5-3.0 unreacted isocyanate groups.

The preferred polyoxyethylene polyols may comprise only recurringoxyethylene units, or may comprise other recurring units provided byother alkylene oxides. Where the polyols comprise more than one type ofoxyalkylene units, the recurring oxyethylene units should be present insufficient amount to provide a satisfactory hydrophilic/hydrophobicbalance and, as indicated above, an oxyethylene content of at least 20mole %, more particularly at least 40 mole %, is preferred. Thepolyoxyethylene polyols can be admixed with other polyols, includinghydrophobic polyols, prior to reaction with the polyisocyanate, againprovided that a satisfactory hydrophilic/hydrophobic balance isprovided.

When the second terminal group is an amine group, the firstwater-soluble monomer is preferably a polyamine and the secondwater-soluble monomer is preferably an aziridene compound. Particularlypreferably, the first water-soluble monomer is ethylenediamine and thesecond water-soluble monomer is aziridene.

In another preferred embodiment, the prepolymer is a copolymer. In thisembodiment, the prepolymer preferably comprises polyvinylpyrrolidone.

Alternatively, the derivatized capped prepolymer may be formed directlyby reacting a water-soluble prepolymer with one or more siloxanecompounds comprising a low-temperature curable group.

After the derivatized capped prepolymer has been chain-extended and theremaining first terminal groups have been reacted with a chaintermination agent, a photoinitiator may be added to the reactionmixture, in an amount from about 0.1% to 5% by weight of the reactioncomposition. Suitable photoinitiators include benzophenone,acetophenone, azobenzene, acenaphthenequinone, o-methoxybenzophenone,thioxanthen-9-one, xanthen-9-one, 7-H-benz(de)anthracen-7-one,1-naphthaldehyde 4,4'-bis(dimethylamino)- benzophenone, fluorene-9-one,1'-acetonaphthone, 2'-acetonaphthone, anthraquinone, 2-tert-butylanthraquinone, 4-aminobenzophenone, 4'-methoxyacetophenone,2,2-diethoxyacetophenone, and benzaldehyde.

The adhesive composition of the present invention is aqueous-based, thatis, the adhesive carrier or solvent includes water in large quantity,including residuum from the preparatory reaction and any amount addedthereafter. In general, the carrier comprises at least 10% water byweight, with a proportion of up to 75% by water typically acceptable. Anadhesive composition according to the present invention can be used asis or, if desired, can be diluted with water, an alcohol, or anotherwater-miscible solvent. The solutions tend to be infinitely dilutablewith alcohols and with water/alcohol mixtures containing about 50% ormore by volume of alcohol. They may also be diluted with water alone toa solid content of about 15% to 20% on a weight basis. As a function ofthe particular adhesive prepared, and of the presence of co-solvents inthe composition, the polymeric adhesive may begin to precipitate belowabout 15% water content.

A major advantage of an adhesive composition within the presentinvention is an ability to be diluted with water and, hence, the abilityto dissolve water-based agents and drugs to form a solid solution,without the agent or drug precipitating or forming an emulsion. A largevariety of water-based drugs, including heat labile drugs, may bedissolved in the compositions of the present invention due to its watermiscibility and low temperature of curing, as is explained below. It iscontemplated that any coagulant, antibiotic, antifungal agent, topicalanesthetic, anti-inflammatory agent or mixture thereof that is watersoluble or water miscible may be dissolved in the adhesive composition.Examples of such agents include an enzyme, a protein, a growth factor, ahormone, a biocidal agent, an antiseptic agent, an antibacterial agent,an antifungal agent, an antiviral agent, an anti-histamine, ananti-inflammatory agent, an anti-pruritic agent, a keratolytic agent, anskin-protective agent, a rubefacient, a topical anesthetic, a hemostaticagent, an anti-anginal agent, a vitamin, a nutritional mineral, awater-soluble polyol compound, collagen or nicotine. In particular,enzymes, such as papain, trypsin, collagenase, subtilisin, ficin,pepsin, lysozyme, streptokinase, fibrinolysin, pinguinain, travase,bromelin and glucose oxidase; antibiotics such as gentamicin sulfate;anti-microbials like polyvinylpyrrolidone-iodine and chlorhexidinedigluconate; growth factors, including platelet-derived growth factor,transforming growth factors-α and -β, fibroblast growth factor,epidermal growth factors and angiogenesis factor; thrombin and otherhemostatic agents; water-soluble cellulose compounds, including alkalimetal salts of carboxymethyl cellulose, hydroxyethyl cellulose; polyolsincluding polyoxyethylene, starch and casein; humectants like gluconicacid and glycerin; vitamins such as B₁, B₂, B₆, B₁₂ and C; minerals,including water-soluble forms of calcium, magnesium, potassium, sulfurand zinc; and nicotine.

An adhesive according to the present invention is particularlywell-suited for use with agents which exist only in water-solution. Forexample, chlorhexidine digluconate is a well-known broad-spectrumantimicrobial that only exists as a water-based compound, i.e.,chlorhexidine digluconate cannot be dried down to a solid. Addition ofchlorhexidine digluconate to a conventional, solvent-based adhesive,which is not water-miscible, would result in an emulsion.

The present invention also contemplates the production of awater-swellable adhesive that is suitable for use in wound dressings andother medical products, especially those that come into contact withbodily fluids. Thus, the uncured adhesive composition of the presentinvention can be spread or coated onto various backings, thereby to formdressings, drapes, tapes and the like, by means well-known to theindustry, such as drawing, rolling and spraying. A preferred backingmaterial in this context is a polyurethane film having a thickness ofbetween about 0.0005 and 0.0015 inch (about 0.00013 to 0.0038 cm). Theadhesive can be uniformly coated onto such film material to a wetthickness of about 001 to 0.003 inch (about 0.0025 to 0.007 cm) anddried at a temperature in the range of 60° C. The film carrying thedried adhesive layer thus obtained is then fully cured, e.g., byexposure to ultraviolet radiation, typically between 219 and 425nanometers. A suitable exposure would be for about 20 seconds at 0.5watts per square centimeter, but equivalent exposures are suitable. Theresult is a dressing with a fully cured, solvent-resistant, waterswellable, transparent adhesive with a MVTR of about 6700 g/m² /24hours.

According to the present invention, a polymer adhesive as describedabove can be applied, preferably after the dissolution thereinto of atleast one bioactive agent, to a flexible backing suitable for a wounddressing or drape, and then is subjected to low-temperature curing, i.e.by cross-linking irradiation. (Before the exposure to actinic radiation,the polymer adhesive is preferably subjected to low-temperature removalof any solvent which is present.) In this manner, the polymer adhesiveis cured to form a single-phase solid retaining the hydrophilic natureof the prepolymer starting material. Alternatively, the polymer adhesivemay be cured on a first substrate and subsequently laminated to a secondsubstrate.

The examples which follow serve further to illustrate the presentinvention.

Example 1. Adhesive Formulation A

Isophorone diisocyanate was reacted with a glycerin-based triol whichwas adducted with ethylene oxide and propylene oxide (molecular weight:10,000). The ethylene oxide was approximately 75 weight-percent of theadduct. The resulting capped prepolymer had an NCO-value of 2.8.Hydroxyethyl methacrylate (HEMA) was added to this capped prepolymer inan amount to react with 80% of the free NCOs and reacted for two hoursunder nitrogen at 35° C. One hundred grams of water were then added to100 grams of the derivatized capped prepolymer. The reaction mixture wasstirred for 60 minutes until an increase in viscosity was noted and someentrapment of carbon dioxide, generated by the reaction, occurred.Ethanol (200 grams) was added to reduce viscosity and the reactionmixture was then stirred for an additional twenty minutes at roomtemperature. Sufficient ammonium hydroxide was then added to halt chainextension, bringing the pH of the mixture to about 10. A photoinitiator,2,2-diethoxyacetophenone, was added to a concentration of 1% of totalcomposition weight. The resulting composition was stable, had lowviscosity and was clear, with approximately 30% non-volatiles. Upondrying and curing by exposure to ultraviolet radiation, a fully curedpressure-sensitive adhesive which swelled in the presence of water wasobtained.

Example 2. Adhesive Formulation B

To the capped prepolymer of Example 1 (NCO-value: 2.8), HEMA was addedto react with 20% of the free NCO groups and reacted for two hours undernitrogen at 35° C. Water (100 grams) was then added to 100 grams of thederivatized capped prepolymer. The reaction mixture was stirred forfifteen minutes until an increase in viscosity was noted and thereoccurred some entrapment of carbon dioxide generated by the reaction.Two hundred grams of ethanol were added, and the reaction mixture wasthen stirred for an additional twenty minutes at room temperature. Thereaction mixture was periodically tested for adhesiveness during thistime by removing small samples, partially drying each sample, andtouch-testing for "tack." Sufficient ammonium hydroxide was then addedto halt chain extension, bringing the pH of the mixture to about 10.After this mixture was completely reacted, 2,2-diethoxyacetophenone wasadded to a concentration of 1% of the total composition weight. Theresulting product was stable, had low viscosity, was clear withapproximately 30% non-volatiles. Upon drying and U.V. curing, a fullycured pressure-sensitive adhesive which swelled in the presence of waterwas obtained.

Example 3. Wound Dressing

A uniform coating of the uncured wet polyurethane adhesive from Example1 was applied to a 1.5 mil-thick (0.0015 inch or 0.0038 cm) polyurethanefilm on a polyethylene liner using a number 25 Mayer rod. The coatingwas then dried at 60° C. for ten minutes. After drying, the adhesivecoated film was exposed to U.V. radiation at 425 nm for five minutes at0.007 watts/cm². The adhesive exhibited excellent tack and swelledmoderately in the presence of water.

Example 4. Wound Dressing

A uniform coating of the uncured wet polyurethane adhesive from Example2 was applied, via a number 25 Mayer rod, to a 1.5 mil-thickpolyurethane film on a polyethylene liner. The coating was then dried at60° C. for ten minutes. After drying, the adhesive-coated film wasexposed to U.V. radiation at 425 nm for five minutes at 0.007 watts/cm².The adhesive exhibited excellent tack and swelled greatly in thepresence of water.

Example 5. Wound Dressing with Antimicrobial

Five grams of a 45% polyvinylpyrrolidoneiodine complex (PVP-I) was addedto 100 ml of the uncured wet polyurethane adhesive formulation ofExample A uniform coating of this polyurethane adhesive was applied to a1.5 mil-thick polyurethane film on a polyethylene liner by means of anumber 25 Mayer rod. The coating was then dried at 60° C. for sixtyminutes. After drying, the adhesive coated film was exposed to U.V.radiation at 425 nm for five minutes at 0.007 watts/cm².

Example 6. Wound Dressing with Antimicrobial

Five grams of a 20% chlorhexidine digluconate water solution was addedto 200 ml of the uncured wet polyurethane adhesive formulation ofExample 1. With a number 25 Mayer rod, a uniform coating of thispolyurethane adhesive was applied to a 1.5 mil-thick polyurethane filmon a polyethylene liner. The coating was then dried at 60° C. for sixtyminutes. After drying, the adhesive-coated film was exposed to U.V.radiation at 425 nm for five minutes at 0.007 watts/cm².

Example 7. Wound Dressing with Antimicrobial

Five grams of a 20% gentamicin water solution was added to 100 ml of theuncured wet polyurethane adhesive formulation of Example 1. A uniformcoating of this polyurethane adhesive was applied to a 'I.5 mil-thickpolyurethane film on a polyethylene liner by means of a number 25 Mayerrod. The coating was then dried at 60° C. for sixty minutes. Afterdrying, the adhesive-coated film was exposed to U.V. radiation at 425 nmfor five minutes at 0.007 watts/cm².

Example 8 Wound Dressing with Coagulant

Five grams of a 20% thrombin water solution was added to 100 ml of theuncured wet polyurethane adhesive formulation of Example 1. A uniformcoating of this polyurethane adhesive was applied to a 1.5 mil-thickpolyurethane film on a polyethylene liner via a number 25 Mayer rod. Thecoating was then dried at 60° C. for sixty minutes. After drying, theadhesive-coated film was exposed to U.V. radiation at 425 nm for fiveminutes at 0.007 watts/cm².

Example 9. Wound Dressing with Protein

One-half gram of a 10% glucose oxidase water solution was added to 100ml of the polyurethane adhesive formulation of Example 1. A uniformcoating of this polyurethane adhesive was applied to a polyurethane film(1.5 mil) on a polyethylene liner by means of a number 25 Mayer rod. Thecoating was then dried at 60° C. for sixty minutes. After drying, theadhesive-coated film was exposed to U.V. radiation at 425 nm for fiveminutes at 0.007 watts/cm².

Example 10. Antimicrobial Activity

The biological activity of the dressing prepared according to Examples 6and 7, respectively, was determined by a "Zone of Inhibition" test,whereby discs of dressing, 19 mm in diameter, were placed on agar (TSA)plates that had been inoculated with 0.5 McFalland standard ofStaphylococcuscus aureus or Escherichia coli. After incubation for 18hours at 37° C., the zones of inhibition of bacterial growth weremeasured and recorded. Control discs for comparison were made followingthe same procedures outlined in Examples 6 and 7 but using anacrylic-based adhesive composition ("MD-0129"; product of Semex MedicalCorp.) or a rubber-based adhesive system ("Nacor 72-9574"; NationalStarch Corp.) in place of the polyurethane-based adhesive composition ofthe present invention. The results are shown below:

    ______________________________________                                        Wound Dressing      S. aureus                                                                              E. coli                                          ______________________________________                                        Example 6           4 mm     4 mm                                             (chlorhexidine digluconate)                                                   Example 7           8 mm     8 mm                                             (gentamicin)                                                                  Acrylic-based adhesive*                                                                           0 mm     0 mm                                             (chlorhexidine digluconate)                                                   Acrylic-based adhesive                                                                            0 mm     0 mm                                             (gentamicin)                                                                  Rubber-based adhesive*                                                                            0 mm     0 mm                                             (chlorhexidine digluconate)                                                   Rubber-based adhesive                                                                             0 mm     0 mm                                             (gentamicin)                                                                  ______________________________________                                         *Coagulation observed                                                    

Example 11. Moisture Vapor Transmission Rate

Ten milliliters of distilled water were contained in a vial having a 1.8cm-diameter opening which was covered with a polyurethane adhesive filmhaving a nominal thickness of 1 mil (0.001 inch or 0.0025 cm). Thearrangement was weighed, at 36° C. (saturated humidity) for 24 hours andreweighed to determine water loss. Moisture vapor permeability rate,expressed in terms of "g/m² /24 hours," was calculated. For comparison,a 1 mil-thick acrylic adhesive film ("TM1620-00"; product of SemexMedical Corp.) and a 1 mil-thick polyisobutylene rubber adhesive film("ARclad"; product of Adhesive Research, Inc.) were tested in the samefashion. The results are as shown below:

    ______________________________________                                        Film Type             MVTR                                                    ______________________________________                                        Polyurethane adhesive film                                                                          6,686                                                   Acrylic adhesive film 2,361                                                   Isobutylene rubber adhesive film                                                                    1,715                                                   Open Vial (no film)   10,229                                                  ______________________________________                                    

Example 12. Water Absorption

The films from Example 11, including the comparison films, were soakedin water, patted dry with a paper towel, and weighed. The films werethen dried in an oven for 1 hour at 60° C. and reweighed. The percentageof water absorption ("absorp. %") was calculated for each film bydividing the difference between the wet (soaked) weight and the dryweight by the dry weight. The results are as shown below:

    ______________________________________                                        Film Type               Absorp. %                                             ______________________________________                                        Polyurethane adhesive film                                                                            397%                                                  Acrylic adhesive film   15.5%                                                 Isobutylene rubber adhesive film                                                                      0.2%                                                  ______________________________________                                    

What is claimed is:
 1. An adhesive composition comprising a polymeradhesive that is soluble or dispersible in water and is low-temperaturecurable to form a solid which is single-phase at ambient temperature,pressure-sensitive, dermatologically acceptable, moisturevapor-permeable, and resistant to dissolution when exposed to water. 2.An adhesive composition as claimed in claim 1, wherein said adhesive,after curing, swells without dissolving when exposed to water.
 3. Anadhesive composition as claimed in claim 1, wherein said polymeradhesive is the product of a process comprising the step of subjecting awater-soluble derivatized capped prepolymer which comprises a pluralityof first terminal groups and a plurality of low-temperature curablegroups to chain extension in the presence of a chain extension agentreactive with said first terminal groups, whereby a polymer is formed,until said polymer attains a determined level of tackiness, when saidchain extension is halted by addition of a chain termination agentreactive with said first terminal groups.
 4. An adhesive composition asclaimed in claim 3, wherein said derivatized capped prepolymer isreacted with an excess, based on the content of said first terminalgroup of said derivatized capped prepolymer, of said chain extensionagent.
 5. An adhesive composition as claimed in claim 3, wherein saidfirst terminal group is an isocyanate group.
 6. An adhesive compositionas claimed in claim 5, wherein said chain extension agent is water, apolyol or a polyamine.
 7. An adhesive composition as claimed in claim 3,wherein said first terminal group is an ester group.
 8. An adhesivecomposition as claimed in claim 7, wherein said chain extension agent isammonia or a polyamine.
 9. An adhesive composition as claimed in claim5, wherein said chain termination agent is ammonia.
 10. An adhesivecomposition as claimed in claim 3, wherein said derivatized cappedprepolymer is formed by reacting a water-soluble capped prepolymercomprising a plurality of said first terminal groups with a derivatizingagent comprising a first functional group which is reactive with saidfirst terminal groups and a second functional group which islow-temperature curable, whereby a portion of said first terminal groupsof said capped prepolymer are reacted with said first functional groupof said derivatizing agent.
 11. An adhesive composition as claimed inclaim 10, wherein said second functional group is capable oflow-temperature cure under the action of actinic radiation, pH shift orfree radicals.
 12. An adhesive composition as claimed in claim 11,wherein said second functional group is an ethylenically unsaturatedgroup.
 13. An adhesive composition as claimed in claim 10, wherein about5 to 80% of said first terminal groups of said capped prepolymer arereacted with said first functional group of said derivatizing agent. 14.An adhesive composition as claimed in claim 13, wherein about 5 to 50%of said first terminal groups of said capped prepolymer are reacted withsaid first functional group of said derivatizing agent.
 15. An adhesivecomposition as claimed in claim 10, wherein said first terminal group isan isocyanate group and said first functional group is a hydroxyl groupor an amine group.
 16. An adhesive composition as claimed in claim 15,wherein said derivatizing agent is a hydroxyalkyl acrylate,methacrylate, crotonate or itaconate.
 17. An adhesive composition asclaimed in claim 10, wherein said first terminal group is an ester groupand said first functional group is an amine group.
 18. An adhesivecomposition as claimed in claim 17, wherein said derivatizing agent isan aminoalkyl amide of a (C₁ -C₆)-α,β-unsaturated carboxylic acid. 19.An adhesive composition as claimed in claim 3, wherein said derivatizedcapped prepolymer is formed by reacting a water-soluble prepolymer withone or more siloxane compounds comprising a low-temperature curablegroup.
 20. An adhesive composition as claimed in claim 10, wherein saidcapped prepolymer is formed by reacting a water-soluble prepolymercomprising a plurality of a second terminal group which is reactive withsaid first terminal group, with a polyfunctional capping agentcomprising a plurality of said first terminal group.
 21. An adhesivecomposition as claimed in claim 20, wherein said first terminal group isan isocyanate group and said second terminal group is a hydroxyl group.22. An adhesive composition as claimed in claim 21, wherein saidprepolymer is a polyoxyalkylene polyol.
 23. An adhesive composition asclaimed in claim 20, wherein said first terminal group is an ester groupand said second terminal group is an amine group.
 24. An adhesivecomposition as claimed in claim 23, wherein said prepolymer is apolyaminoalkylene polyamine.
 25. An adhesive composition as claimed inclaim 20, wherein said prepolymer is formed by reacting a firstwater-soluble monomer comprising a plurality of said second terminalgroup with a second water-soluble monomer reactive with said secondterminal group.
 26. An adhesive composition as claimed in claim 25,wherein said second terminal group is a hydroxyl group.
 27. An adhesivecomposition as claimed in claim 26, wherein said first water-solublemonomer is a polyol and said second water-soluble monomer is an epoxidecompound.
 28. An adhesive composition as claimed in claim 27, whereinsaid polyol is ethylene glycol, glycerol, trimethylolpropane orpentaerythritol.
 29. An adhesive composition as claimed in claim 28,wherein said first water-soluble monomer is ethylene glycol, glycerol ora mixture of ethylene glycol and glycerol and said second water-solublemonomer is ethylene oxide.
 30. An adhesive composition as claimed inclaim 28, wherein said prepolymer has a molecular weight of about 3 to15 kilodaltons.
 31. An adhesive composition as claimed in claim 27,wherein said prepolymer is a copolymer which comprises at least 20% byweight of ethylene oxide moieties.
 32. An adhesive composition asclaimed in claim 25, wherein said second terminal group is an aminegroup.
 33. An adhesive composition as claimed in claim 32, wherein saidfirst water-soluble monomer is a polyamine and said second water-solublemonomer is an aziridene compound.
 34. An adhesive composition as claimedin claim 20, wherein said prepolymer is a copolymer.
 35. An adhesivecomposition as claimed in claim 34, wherein said copolymer comprisespolyvinylpyrrolidone.
 36. An adhesive composition as claimed in claim 1,wherein said polymer adhesive is the product of a process comprising thesteps ofi) reacting a compound comprising a plurality of hydroxyl groupsand a polyisocyanate compound to form an isocyanate-terminatedpolyurethane capped prepolymer, ii) reacting a portion of the terminalisocyanate groups of said polyurethane capped prepolymer with aderivatizing agent comprising a group reactive with isocyanate and alow-temperature curable group to form a derivatized capped prepolymer,and iii) reacting said derivatized capped prepolymer with a chainextension agent reactive with isocyanate to effect chain extension ofsaid derivatized capped prepolymer, whereby a polymer is formed, untilsaid polymer attains a determined level of tackiness, wherein said chainextension is halted by addition of a chain termination agent reactivewith isocyanate.
 37. An adhesive composition as claimed in claim 1,further comprising a bioactive agent dissolved therein.
 38. A adhesivecomposition as claimed in claim 37, wherein said bioactive agent issoluble in or miscible with water.
 39. An adhesive composition asclaimed in claim 37, wherein said bioactive agent is a protein, anenzyme, a growth factor, a hormone, a biocidal agent, an antisepticagent, an antibacterial agent, an antifungal agent, an antiviral agent,an anti-histamine, an anti-inflammatory agent, an anti-pruritic agent, akeratolytic agent, an skin-protective agent, a rubefacient, a topicalanesthetic, a hemostatic agent, an anti-anginal agent, a vitamin, anutritional mineral, a water-soluble cellulose compound, collagen ornicotine.
 40. A dermatologically-acceptable, moisture vapor-permeable,pressure-sensitive adhesive composition that is a single-phase solid atambient temperature and resists dissolution when exposed to water,comprising a polymer adhesive which is the product of a processcomprising the steps ofi) providing a water-soluble derivatized cappedprepolymer which comprises a first terminal group and a low-temperaturecurable group, ii) subjecting said water-soluble derivatized cappedprepolymer to chain extension in the presence of a chain extension agentreactive with said first terminal group, whereby a polymer is formed,until said polymer attains a determined level of tackiness, when saidchain extension is halted by addition of a chain termination agentreactive with said first terminal groups, and iii) subjecting saidpolymer to low-temperature curing.
 41. An adhesive composition asclaimed in claim 40, wherein in step iii, said low-temperature curing iseffected by exposure to ultraviolet radiation or an electron beam. 42.An adhesive composition as claimed in claim 40, further comprising abioactive agent dissolved therein.
 43. An adhesive composition asclaimed in soluble.
 44. A water vapor-permeable, pressure-sensitiveadhesive wound dressing, comprising a flexible backing coated with apressure-sensitive adhesive layer provided on at least a portion of thesurface of said backing, wherein said adhesive layer comprises anadhesive composition as claimed in claim
 40. 45. A wound dressing asclaimed in claim 44, wherein a bioactive agent is dissolved in saidadhesive layer.
 46. A wound dressing as claimed in claim 45, whereinsaid bioactive agent is water-soluble.
 47. A wound dressing as claimedin claim 44, wherein said adhesive layer has moisture vapor permeabilityof about 6700 g/m² /24 hours.
 48. A wound dressing as claimed in claim44, wherein said flexible backing is a polyurethane film.
 49. A processfor producing a water vapor-permeable, pressure-sensitive adhesive wounddressing which comprises the steps ofi) providing a flexible backing,ii) applying to at least a portion of the surface of said backing anadhesive composition as claimed in claim 3, and iii) subjecting saidadhesive composition to low-temperature cure.
 50. A process forproducing a polymer adhesive that is soluble or dispersible in water andis low-temperature curable to form a solid which is single-phase atambient temperature, pressure-sensitive, dermatologically acceptable,moisture vapor-permeable, and resistant to dissolution when exposed towater, which comprises the steps ofi) providing a derivatized cappedprepolymer comprising a plurality of first terminal groups, and ii)reacting said derivatized capped prepolymer with a chain extension agentreactive with said first terminal groups to effect chain extension ofsaid derivatized capped prepolymer, whereby a polymer is formed, untilsaid polymer attains a determined level of tackiness, when said chainextension is halted by addition of a chain termination agent reactivewith said first terminal groups.
 51. A process for producing a polymeradhesive that is soluble or dispersible in water and is low-temperaturecurable to form a solid which is single-phase at ambient temperature,pressure-sensitive, dermatologically acceptable, moisturevapor-permeable, and resistant to dissolution when exposed to water,which comprises the steps ofi) reacting a compound comprising aplurality of hydroxyl groups and a polyisocyanate compound to form anisocyanate-terminated polyurethane capped prepolymer, ii) reacting aportion of the terminal isocyanate groups of said polyurethane cappedprepolymer with a derivatizing agent comprising a group reactive withisocyanate and a low-temperature curable group to form a derivatizedcapped prepolymer, and iii) reacting said derivatized capped prepolymerwith a chain extension agent reactive with isocyanate to effect chainextension of said derivatized capped prepolymer, whereby a polymer isformed, until said polymer attains a determined level of tackiness, whensaid chain extension is halted by addition of a chain termination agentreactive with isocyanate.
 52. A process for producing adermatologically-acceptable, moisture vapor-permeable,pressure-sensitive adhesive composition that is a single-phase solid atambient temperature and resists dissolution when exposed to water, whichcomprises the step of subjecting a polymer adhesive produced by aprocess as claimed in claim 50 to low-temperature cure.
 53. A processfor producing a dermatologically-acceptable, moisture vapor-permeable,pressure-sensitive adhesive composition that is a single-phase solid atambient temperature and resists dissolution when exposed to water, whichcomprises the step of subjecting a polymer adhesive produced by aprocess as claimed in claim 51 to low-temperature cure.